1. Team 3 Morning Report
Thursday, July 11, 2018

2. HPI
55 y/o male
PMH: Depression, HLD, Methamphetamine abuse, Chronic Hepatitis C
2 days of worsening hand swelling
Swelling began in his wrist and now extends from his hand to his elbow
Range of motion is limited, unable to close fist fully
He reports pain 8/10 in his arm.
intermittent fevers, chills
He denies numbness. Denies chest pain, shortness of breath, nausea, vomiting, diarrhea, constipation.
He is not currently taking any medications.

3. Objective data and LABS
Afebrile.
Vitals are WNL.
WBC blood cell count is 14,000.
CBC and BMP are otherwise WNL.
Chest x-ray normal.
X-ray of arm shows no sign of osteomyelitis or subcutaneous gas.

4. Differential?

5. Cellulitis
manifests as an area of skin erythema, edema, and warmth; it develops as a result of bacterial entry via breaches in the skin barrier
nearly always unilateral
Misdiagnosis is common
Predisposing factors:
diabetes, HIV, edema due to venous insufficiency, preexisting skin infection, edema due to impaired lymphatic drainage

6. Common Bugs involved in cellulitis
The most common cause of cellulitis is beta-hemolytic streptococci (groups A, B, C, G, and F), most commonly group A Strep or Strep pyogenes; S. aureus (including methicillin-resistant strains) is a notable but less common cause Gram-negative aerobic bacilli are identified in a minority of cases.
Less common causes of cellulitis include Haemophilus influenzae (buccal cellulitis), clostridia and non-spore-forming anaerobes (crepitant cellulitis), Streptococcus pneumoniae, and Neisseria meningitidis. In immunocompromised patients, the spectrum of potential pathogens is much broader, and infectious disease consultation is warranted.

7. Cellulitis vs. erysipelas
Cellulitis involves the deeper dermis and subcutaneous fat. May present with or without purulence. Usually a more indolent course with development of localized symptoms over a few days.
Erysipelas involves the upper dermis and superficial lymphatics. Nonpurulent. Generally acute onset of symptoms with systemic manifestations, including fever, chills, severe malaise, headache. Clear demarcation between involved and uninvolved tissue . Involvement of the ear (Milian's ear sign) is a distinguishing feature for erysipelas, since this region does not contain deeper dermis tissue.
Additional manifestations of both:
Lymphangitis and enlargement of regional lymph nodes. Edema surrounding the hair follicles may lead to dimpling in the skin, creating a "peau d'orange“appearance. Vesicles, bullae, and ecchymoses or petechiae may be observed. Crepitant and gangrenous cellulitis are unusual manifestations of cellulitis due to clostridia and other anaerobes.
Severe manifestations with systemic toxicity should prompt investigation for additional underlying sources of infection.

8. Cellulitis is often confused with other conditions
Necrotizing fasciitis: Pain out of proportion to exam, progressive destruction of the muscle fascia
Toxic shock syndrome: local swelling and erythema ecchymoses and sloughing of skin. May be normotensive on presentation but subsequently become hypotensive.
Gas gangrene: presence of tissue crepitus favors clostridial infection, severe pain, setting of surgery or trauma
Erythema migrans: Erythema migrans is an early manifestation of Lyme disease; it consists of a region of erythema at the site of a tick bite, often with central clearing and a necrotic center. The diagnosis is established based on serologic testing, although sensitivity in early disease is low. 

9. Toxic Shock Syndrome
Necrotizing fasciitis
Gas Gangrene

10. Noninfectious conditions that can look like cellulitis
Stasis Dermatitis
Acute Gout
Contact Dermatitis
Deep vein thrombosis

11. Treatment: Parenteral vs. oral
Mild infection may be treated with an oral antibiotic regimen.
Patients with signs of systemic toxicity or rapid progression of erythema be treated initially with parenteral antibiotics .
Parenteral therapy is also appropriate for patients with persistence or progression of symptoms despite 48 hours of oral antibiotic therapy, inability to tolerate oral therapy, or proximity of the lesion to an indwelling medical device such as a prosthetic joint or vascular graft

12. ANTIBIOTIC CHOICE
Concern for MRSA with a purulent infection:  clindamycin, TMP-SMX, or tetracyclines: doxycycline or minocycline
Oxazolidinones (linezolid or tedizolid) and delafloxacin are additional agents with activity against MRSA; they should be reserved for circumstances in which none of the other regimens listed can be used, and careful monitoring is required.
Antimicrobial therapy with activity against MRSA and beta-hemolytic streptococci may be achieved with clindamycin or TMP-SMX monotherapy; there may be regional differences in MRSA susceptibility to these agents
Because of uncertain streptococcal coverage with doxycycline or minocycline, we add amoxicillin to each of these agents to ensure adequate antistreptococcal activity.

14. Parenteral Therapy
Options for empiric parenteral therapy of MRSA include vancomycin and daptomycin.
Alternative parenteral agents with activity against MRSA include linezolid, delafloxacin, ceftaroline among others. These agents also have activity against beta-hemolytic Streptococcus.

16. Duration of therapy
Patients with mild infection who warrant outpatient management with oral antibiotic therapy should have repeat evaluation after 24 to 48 hours to verify clinical response.
Patients with MRSA responsive to oral therapy are typically treated for 5 days; extension of the duration (up to 14 days) may be warranted in the setting of severe infection, slow response to therapy, or immunosuppression. Lack of response may be due to infection with resistant organism(s), inadequate adherence, or presence of a deeper, more serious infection than previously realized.
Patients with infection warranting parenteral therapy (in the absence of bacteremia or involvement beyond soft tissue) are typically treated for a total duration of 5 to 14 days. Once there are signs of clinical improvement with no evidence of systemic toxicity, antibiotics may be transitioned from parenteral to oral therapy.

19. DURATION Mild Infection:
Can be treated initially with oral antibiotics
Close monitoring for clinical improvement. Cellulitis usually responds to 5 days of therapy. The duration may be extended to up to 14 days if needed.
Severe Infection:
Should receive intravenous antibiotics. Intravenous therapy may be switched to outpatient oral therapy when evidence of clinical improvement is apparent
Patients with involvement limited to the soft tissues may be treated with 5 to 14 days of therapy.
Bacteremia, 10 to 14 days of parenteral therapy should be administered. Patients with complicated infections (such as synovitis or osteomyelitis): prolonged therapy

20. Non-Purulent cellulitis
Prospective:
179 adults admitted to LA county hospital w/ diffuse non-purulent cellulitis
73% were due to beta-hemolytic streptococci, as confirmed by cultures, antistreptolysin-O or anti-DNase-B antibodies
No etiology identified in 27% of cases
Overall response rate to beta-lactam therapy was 96%

21. Purulent Cellulitis
Prospective study across 11 emergency departments in 2004 
422 adults presenting with purulent skin and soft tissue infections
76% of infections due to Staph aureus. 59% due to MRSA.
Cover for MRSA in a purulent cellulitis

22. Vancomycin + Pip/tazo (zosyn)
Prospective multicenter study
242 hospitalized adults who received 72 or more hours of IV vancomycin + pip/tazo or vanc + cefepime/meropenem
Pt’s receiving vancomycin + pip/tazo were 6.7x more likely to develop AKI than other cohort

23. When to expand coverage?
Purulent cellulitis
Cover gram negatives and anaerobes if:
Perioral or perirectal location of abscess
Pressure ulcer
Prominent skin necrosis

24. Treatment response:
Cellulitis will worsen for a day, stabilize for a day, then start to improve.
Some patients are slow responders.
Who to anticipate being a slow responder? 
Female sex
Cardiovascular disease
Higher BMI
Cellulitis other than erysipelas
Clin Infect Dis. 2016 Oct 15;63(8): doi: /cid/ciw463. Epub 2016 Jul 11.
Early Response in Cellulitis: A Prospective Study of Dynamics and Predictors.